Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

INITIAL

hypernatraemia at any stage

1st line – oral/intravenous fluids

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INITIAL
|
hypernatraemia at any stage
1st line – 

oral/intravenous fluids

Hypotonic fluid replacement is required. Oral and enteral fluid is preferred if possible. Intravenous 5% dextrose and 0.45% sodium chloride may be necessary. The infusion rates are determined by choice of infusate, degree of hypernatraemia, the desired rate of correction, and the estimated deficit in total body water.[55]

Regular serum sodium tests are required.

If the hypernatraemia is acute, reducing the serum sodium concentration by up to 1 mmol/L (1 mEq/L) per hour may be appropriate.[55]

If the hypernatraemia is long-standing or is of uncertain duration, the rate of correction should be at a maximal rate of 0.5 mmol/L (0.5 mEq/L) per hour.

Decrease in serum sodium should be limited to 10 mmol/L (10 mEq/L) per 24 hours, to a target serum sodium of 145 mmol/L (145 mEq/L).[55]

ACUTE

acute arginine vasopressin deficiency (AVP-D)

1st line – desmopressin

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ACUTE
|
acute arginine vasopressin deficiency (AVP-D)
|
no history of recent pituitary surgery or trauma
1st line – 

desmopressin

Treatment is with parenteral or oral desmopressin (a synthetic, long-acting analogue of arginine vasopressin [AVP], also known as DDAVP).

Treatment is started at the lowest possible dose, with subsequent dose titration based upon clinical and biochemical response.​[61]

Primary options

desmopressin: children <4 years of age: 0.1 to 0.8 mg/day orally given in 2 divided doses; children 4-12 years of age: 0.1 to 1.2 mg/day orally given in 2-3 divided doses; children ≥12 years of age and adults: 0.1 to 1.2 mg/day orally given in 2-3 divided doses, or 2-4 micrograms/day subcutaneously/intravenously given in 1-2 divided doses

Consider – oral/intravenous fluids

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ACUTE
|
acute arginine vasopressin deficiency (AVP-D)
|
no history of recent pituitary surgery or trauma
Consider – 

oral/intravenous fluids

Additional treatment recommended for SOME patients in selected patient group

Patients who are conscious should be encouraged to drink.

Intravenous 5% dextrose and 0.45% sodium chloride may be necessary in some patients.

Frequent electrolyte assessments are required to manage the clinical situation safely.

Lower rates of fluid administration may be required in patients treated with desmopressin in parallel with intravenous fluids.

Serum sodium should be corrected at a maximal rate of 0.5 mmol/L (0.5 mEq/L) per hour. The decrease in serum sodium should be limited to 10 mmol/L (10 mEq/L) over 24 hours, to target nadir of 145 mmol/L (145 mEq/L).[55]

1st line – desmopressin

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ACUTE
|
acute arginine vasopressin deficiency (AVP-D)
|
recent pituitary surgery or trauma
1st line – 

desmopressin

If polyuria is present, urine osmolality is low, or if hypernatraemia is present, AVP-D is likely and treatment should be given with desmopressin (a synthetic, long-acting analogue of arginine vasopressin [AVP], also known as DDAVP).

Patients should be started at the lowest possible dose, with subsequent titration based upon clinical and biochemical response.​[61]​ As postoperative AVP-D is often transient initially, desmopressin should be prescribed on an ‘as required’ basis according to urine output and electrolyte assessment.

There is also a risk of the triple phase response with initial AVP-D, followed by transient syndrome of inappropriate antidiuresis.[12] Permanent AVP-D or return to normal function may follow. It is thus key to monitor fluid balance and sodium carefully.

Primary options

desmopressin: children <4 years of age: 0.1 to 0.8 mg/day orally given in 2 divided doses; children 4-12 years of age: 0.1 to 1.2 mg/day orally given in 2-3 divided doses; children ≥12 years of age and adults: 0.1 to 1.2 mg/day orally given in 2-3 divided doses, or 2-4 micrograms/day subcutaneously/intravenously given in 1-2 divided doses

Consider – oral/intravenous fluids

Back
ACUTE
|
acute arginine vasopressin deficiency (AVP-D)
|
recent pituitary surgery or trauma
Consider – 

oral/intravenous fluids

Additional treatment recommended for SOME patients in selected patient group

Patients who are conscious should be encouraged to drink.

Intravenous 5% dextrose and 0.45% sodium chloride may be necessary in some patients.

Frequent electrolyte assessments are required to manage the clinical situation safely.

Lower rates of fluid administration may be required in patients treated with desmopressin in parallel with intravenous fluids.

Serum sodium should be corrected at a maximal rate of 0.5 mmol/L (0.5 mEq/L) per hour. The decrease in serum sodium should be limited to 10 mmol/L (10 mEq/L) over 24 hours, to target nadir of 145 mmol/L (145 mEq/L).[55]

ONGOING

chronic arginine vasopressin deficiency (AVP-D)

1st line – desmopressin

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ONGOING
|
chronic arginine vasopressin deficiency (AVP-D)
1st line – 

desmopressin

The treatment of choice is the synthetic, long-acting arginine vasopressin (AVP) analogue desmopressin (also known as DDAVP).[62] Oral, intranasal, and parenteral formulations are available. Patient preference is important in choosing formulation, and an individualised dosing schedule is required.

Treatment should be started at low dose, with increments based on response and serum sodium test results. The average duration of action per dose is 6 to 18 hours.

In some patients with mild AVP-D, a single night-time dose is sufficient to control symptoms.[3]

Treatment of AVP-D in small children is challenging. Rapid changes in serum osmolality can occur.[61]

Patients may be advised to delay, reduce, or omit treatment on 1 day per week, to allow off-loading of excess water and prevent hyponatraemia, which is common.[63]

Primary options

desmopressin: children <4 years of age: 0.1 to 0.8 mg/day orally given in 2 divided doses; children 4-12 years of age: 0.1 to 1.2 mg/day orally given in 2-3 divided doses; children ≥12 years of age and adults: 0.1 to 1.2 mg/day orally given in 2-3 divided doses, or 2-4 micrograms/day subcutaneously/intravenously given in 1-2 divided doses

OR

desmopressin nasal: (0.01%) children ≥3 months of age: 5-30 micrograms/day intranasally given in 1-2 divided doses; children ≥12 years of age and adults: 10-40 micrograms/day intranasally given in 1-3 divided doses

arginine vasopressin resistance (AVP-R)

1st line – maintenance of adequate fluid intake

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ONGOING
|
arginine vasopressin resistance (AVP-R)
1st line – 

maintenance of adequate fluid intake

The mainstay of treatment is adequate fluid intake to match output and insensible losses.

Adequate intake may be difficult in intercurrent illness, as urinary excretion may be as much as 12 litres per day.[10]

Plus – treatment of underlying cause

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ONGOING
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arginine vasopressin resistance (AVP-R)
Plus – 

treatment of underlying cause

Treatment recommended for ALL patients in selected patient group

Any underlying cause, if identified, should be corrected.

Drug-induced AVP-R may resolve following discontinuation of the offending drug.[64] AVP-R secondary to lithium may be irreversible.[41]

Any underlying renal disease should be treated.

AVP-R secondary to hypercalcaemia or hypokalaemia should resolve following treatment of the electrolyte disorder.

Consider – sodium restriction and/or pharmacotherapy

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ONGOING
|
arginine vasopressin resistance (AVP-R)
Consider – 

sodium restriction and/or pharmacotherapy

Additional treatment recommended for SOME patients in selected patient group

Low-sodium diet (<500 mg/day), thiazide diuretics, or indometacin may reduce urine output.​[1][53]

As these agents may act synergistically, combination therapy can be used.

Given the potential for dehydration and nephrotoxicity, a nephrology specialist should be consulted if pharmacotherapy is considered.

Primary options

hydrochlorothiazide: children: 1-3 mg/kg/day orally given in 2 divided doses; adults: 12.5 to 50 mg orally once daily

OR

indometacin: children ≥2 years of age: 2 mg/kg/day orally given in 2-4 divided doses, maximum 150 mg/day; adults: 25-50 mg orally two to three times daily, maximum 200 mg/day

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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